ABSTRACT The prevention and treatment of obesity and mental health disorders in adolescence are two major public health problems in the United States (U.S.) today. The incidence of adolescents who are overweight or obese has increased dramatically over the past 20 years, with approximately 17.1 percent of teens now being overweight or obese. Furthermore, approximately 15 million children and adolescents (25 percent) in the U.S. have a mental health problem that is interfering with their functioning at home or at school, but less than 25 percent of those affected receive any treatment for these disorders. The prevalence rates of obesity and mental health problems are even higher in Hispanic teens, with studies suggesting that the two conditions often coexist in many youth. However, despite the rapidly increasing incidence of these two public health problems with their related health disparities and adverse health outcomes, there has been a paucity of theory- based intervention studies conducted with adolescents in high schools to improve their healthy lifestyle behaviors as well as their physical and mental health outcomes. Unfortunately, physical and mental health services continue to be largely separated instead of integrated in the nation's healthcare system, which often leads to inadequate identification and treatment of these significant adolescent health problems. Therefore, the goal of the proposed randomized controlled trial is to test the efficacy of the COPE (Creating Opportunities for Personal Empowerment)/Healthy Lifestyles TEEN (Thinking, Feeling, Emotions & Exercise) Program, an educational and cognitive-behavioral skills building intervention guided by cognitive behavior theory, on the healthy lifestyle behaviors and depressive symptoms of 800 culturally diverse adolescents enrolled in Phoenix, Arizona high schools. The specific aims of the study are to: (1) Use a randomized controlled trial to test the short- and more long-term efficacy of the COPE TEEN Program on key outcomes, including healthy lifestyles behaviors, depressive symptoms and body mass index percentage, (2) Examine the role of cognitive beliefs and perceived difficulty in leading a healthy lifestyle in mediating the effects of COPE on healthy lifestyle behaviors and depressive symptoms; and (3) Explore variables that may moderate the effects of the intervention on healthy lifestyle behaviors and depressive symptoms, including race/ethnicity, gender, SES, acculturation, and parental healthy lifestyle beliefs and behaviors. Six prior pilot studies support the need for this full scale clinical trial and the use of cognitive-behavioral skills building in promoting healthy lifestyles beliefs, behaviors and optimal mental health in teens. This study is consistent with the NIH roadmap and goals of improving people's health and preventing the onset of disease and disability as well as promoting the highest level of health in a vulnerable population.